Crystal Surface Reactivity of Esterase@Zeolitic Imidazolate Framework Biocomposites

Abstract

Esterase@zeolitic imidazolate framework (Esterase@ZIF) biocomposites have been synthesized by biomineralization of pig liver esterase to explore the synergistic interplay between esterase and the ZIF framework on crystal surface reactivity and biocompatibility. The targeted Esterase@ZIF crystal phases cover a wide range of ZIF topologies, namely, Zn(mIm)2 (ZIF-8, 3D sodalite, microporous, mImH = 2-methylimidazole), Zn(mIm)2·(mImH)0.5 (ZIF-L, 2D layered, nonporous), and Zn(mIm)(CO3)0.5 (ZIF-C, 3D, nonporous). As model reactions, we have assessed the hydrolytic decontamination of the G-type nerve agent simulant diisopropylfluorophosphate (DIFP) and esterase activity toward indoxyl acetate hydrolysis. The results show a clear synergistic interplay between esterase and the ZIF framework, which is attributed to the stabilized open-lid conformation of esterase and the reactivity of the ZIF crystal surface, leading to enhanced hydrolytic activity. P–F bond hydrolysis also induces Esterase@ZIF crystal surface degradation releasing mImH and Zn2+ ions. Released imidazole moieties enable a nucleophilic attack to DIFP-inhibited acetylcholinesterase (DIFP@AChE), promoting AChE reactivation and thereby reversing organophosphorous poisoning. In vitro cytotoxicity assays toward human neuroblastoma cell lines are indicative of increased biocompatibility of Esterase@ZIF in comparison to pristine ZIF materials. These results also exemplify that biomineralization can be used not only to protect enzymes from harsh environments but to modulate crystal surface reactivity and biocompatibility.